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WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors

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  • Fariba Jian Motamedi

    (Institute of Biology Valrose, Université de Nice-Sophia
    Inserm, UMR1091
    CNRS, UMR7277)

  • Danielle A. Badro

    (Institute of Biology Valrose, Université de Nice-Sophia
    Inserm, UMR1091
    CNRS, UMR7277)

  • Michael Clarkson

    (Institute of Biology Valrose, Université de Nice-Sophia
    Inserm, UMR1091
    CNRS, UMR7277)

  • M Rita Lecca

    (Institute of Pharmaceutical Sciences, ETH Zurich
    Functional Genomics Center Zurich, UZH/ETH Zurich)

  • Stephen T. Bradford

    (Institute of Biology Valrose, Université de Nice-Sophia
    Inserm, UMR1091
    CNRS, UMR7277
    Garvan Institute of Medical Research)

  • Fabian A. Buske

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, University of NSW Australia)

  • Kathrin Saar

    (MDC for Molecular Medicine)

  • Norbert Hübner

    (MDC for Molecular Medicine)

  • André W. Brändli

    (Institute of Pharmaceutical Sciences, ETH Zurich
    Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians-University)

  • Andreas Schedl

    (Institute of Biology Valrose, Université de Nice-Sophia
    Inserm, UMR1091
    CNRS, UMR7277)

Abstract

Kidney organogenesis requires the tight control of proliferation, differentiation and apoptosis of renal progenitor cells. How the balance between these cellular decisions is achieved remains elusive. The Wilms’ tumour suppressor Wt1 is required for progenitor survival, but the molecular cause for renal agenesis in mutants is poorly understood. Here we demonstrate that lack of Wt1 abolishes fibroblast growth factor (FGF) and induces BMP/pSMAD signalling within the metanephric mesenchyme. Addition of recombinant FGFs or inhibition of pSMAD signalling rescues progenitor cell apoptosis induced by the loss of Wt1. We further show that recombinant BMP4, but not BMP7, induces an apoptotic response within the early kidney that can be suppressed by simultaneous addition of FGFs. These data reveal a hitherto unknown sensitivity of early renal progenitors to pSMAD signalling, establishes FGF and pSMAD signalling as antagonistic forces in early kidney development and places WT1 as a key regulator of pro-survival FGF signalling pathway genes.

Suggested Citation

  • Fariba Jian Motamedi & Danielle A. Badro & Michael Clarkson & M Rita Lecca & Stephen T. Bradford & Fabian A. Buske & Kathrin Saar & Norbert Hübner & André W. Brändli & Andreas Schedl, 2014. "WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5444
    DOI: 10.1038/ncomms5444
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